FIELD OF THE INVENTION
[0001] The present invention is related to a nebulizer, more particularly to a novel operated
nebulizer, comprising an air actuator adapted for releasing a flow of compressed air
at such time as a predetermined pressure has been reached and further a nozzles system
for medication distribution having a predetermined droplets size.
BACKGROUND OF THE INVENTION
[0002] Inhaled medication is the first-line treatment of diseases such as asthma or chronic
obstructive pulmonary disease. Its effectiveness is related to the amount of drug
deposited beyond the oropharyngeal region, the place where the deposit occurs and
its distribution. It is further important to consider the size of the inhaled particles,
the breathing conditions, the geometry of the airways, and the mucociliary clearance
mechanisms.
[0003] Nebulizers allow high doses administration of medication in patients who are not
able to coordinate or cooperate and they are further able to administer several substances
mixed together in one same solution. It is known that the minimal inspiratory flow
needed for the aerosol produced by a nebulizer to reach the lungs is about 6-8 l/min.
However, there are high amounts of drug lost as much of the medication is retained
in the nebulizer dead-space, or it is lost in the room air during expiration. It has
further been estimated that only 10% of the dose that is initially placed in the nebulizer
will be effectively deposited in the lungs. The large droplets are deposited in the
oropharynx, while the droplets are too small to penetrate in the lungs and are once
again expelled during expiration.
[0004] US patent app. No 2005247305 discloses a nebulizer having an insertable container and a monitoring device for
counting actuations of the nebulizer is proposed. The monitoring device is mounted
in a detachable housing part and directly detects movements of container during a
nebulizing process, an air supply current in the region of a mouthpiece, and/or the
production of aerosol, in order to detect this as the actual dispensing of fluid and
actuation of the nebulizer, while preferably the time of actuation of the nebulizer
is additionally detected and stored. This allows better monitoring and guidance for
the user.
[0005] US patent application No. 2007282276 presents a process and a device for dosing a pharmaceutical agent in particular as
an aerosol, with enhanced dosing accuracy. To achieve an enhanced dosing accuracy,
a first component is produced in batches and combined with a second component, such
as a guide pipe selected from a suitable group guide pipes. The suitable group of
second components is selected based on at least one decisively significant value of
the respective batch first components and is distinguished by an essential value of
the second component which will optimize the sealing between the first and second
components.
[0006] WO2013098334 discloses a device for enabling a user to inhale at a desired inspiratory flow rate
and/or pressure, comprising a feedback system configured to indicate to a user by
means of a signal during an inhalation manoeuvre whether an inhalation parameter,
such as the inspiratory flow rate, is within a predefined target range. The signal
may be an optical or a non-optical signal, such as a light signal, an acoustic signal,
or a tactile signal.
[0007] US patent application No. 2006201499 discloses a device for the application of a pharmaceutical via the lung comprising
a control and an air pump connected to the control, the air pump being controlled
by the control such that it supplies an inhalation flow, or inhalation volume or both
according to a predetermined time course to a nebulizer connected to the air pump.
[0008] US patent no. 3788525 discloses a compressed air aspirating and propellant actuated dispenser for dispensing
fluid products. A valve assembly has a compressed air flow path therethrough with
a valve member obturating the compressed air flow path. A product containing means
in the device is connected to the aspirating means by a product flow path. A hollow
enclosure surrounds the other end of the compressed air flow path and a piston is
movable in the hollow enclosure toward the valve and engagable with the valve member
after it has moved into the hollow enclosure for actuating the valve member for opening
the compressed air flow path. An aerosol propellant cartridge having a spring loaded
dispensing valve is mounted on the device for movement relative thereto for opening
said dispensing valve, the dispensing valve being directed into the hollow enclosure
for moving the piston into the hollow enclosure. When the device is moved relative
to the cartridge, propellant dispensed into the hollow enclosure drives the piston
to compress air in the hollow enclosure ahead of the piston and the piston engages
the valve member after it has moved into the enclosure sufficiently far to build up
the desired pressure of air within the enclosure in order to open the valve member
to allow the compressed air to flow along the compressed air flow path. The propellant
is then vented away from the point of product dispensing.
[0009] WO13065503 discloses a liquid atomization device which includes a first gas spray unit and a
second gas spray unit; a liquid outflow unit for flowing out liquid; a gas-liquid
mixing area where a gas flow sprayed from the first gas spray unit, a gas flow sprayed
from the second gas spray unit, and liquid which flows out from the liquid outflow
unit are made to collide against each other to atomize the liquid; a projection formed
to project out of the device such that its cross section projects in a convex manner,
the gas-liquid mixing area being formed in the projection; a spray slit formed in
the projection along a wide angle spray direction of mist produced by the gas-liquid
mixing area; and a restriction portion formed near a bottom of the spray slit such
that the restriction portion inclines in the wide angle spray direction of the mist.
[0010] The above-described devices do not provide a drug deposition having a defined particle
size thus, provide a long treatment time.
[0011] It therefore remains a long felt and unmet need to provide novel means and methods
for a nebulizer device which allows the deposition of inhaled drugs in more effective
and short term manner based on the size of the drug particles.
SUMMARY OF THE INVENTION
[0012] It is an object of the present invention to provide a nebulizer for dispensing a
dose of a medicament according to claim 1. Preferred embodiments are mentioned in
the subclaims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] In the following description of the preferred embodiments, reference is made to the
accompanying drawings that form a part hereof, and in which are shown by way of illustration
specific embodiments in which the invention may be practiced. It is understood that
other embodiments may be utilized and structural changes may be made without departing
from the scope of the present invention. The present invention may be practiced according
to the claims without some or all of the further additional specific details described
hereunder. For the purpose of clarity, technical material that is known in the technical
fields related to the invention has not been described in detail so that the present
invention is not unnecessarily obscured.
[0014] In the accompanying drawing: FIGs. 1A-B
[0015] present a schematic view of a nebulizer system of the present invention;
FIGs. 2A-C present a schematic view of an air pressure-operated nebulizer for spraying a burst
of dose forms, of the present invention;
FIGs. 3A-3B present a cross section of the venturi system of the nebulizer of the present invention;
FIGs. 4A-4B illustrate a cross section of the nozzles system for dispensing a consecutively dose
of a medicament in the form of a mist, of the present invention;
FIGs. 5A-5D illustrate a cross section of the nozzles system for dispensing a consecutively dose
of a medicament in the form of a mist, of the present invention; and,
FIGs. 6-19 present graphs of a medication droplets distribution of the nebulizer comprising
a dual nozzle, of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0016] The present invention have been defined specifically to provide device, means and
method for a nebulizer device and system for spraying a dose form, comprising: a gaseous
propellant, actuator means configured to release a flow of compressed air after a
predetermined liquefied gas (LG) pressure has been reached and, an air outlet. The
actuator means operated by the activated liquefied gas (LG) pressure in order to compress
air via the air outlet. The actuator means builds up a pressure on the air delivery
side for causing a dose of airflow.
[0017] The present invention provides a nebulizer drug delivery system which improves lung
deposition whilst at same time, increase lung bioavailability hence, overall systemic
absorption. The nebulizer of the present invention further solves the problem of nebulizers
which deliver medication continuously by using the patient's breathing cycle to automatically
control the delivery of medication to patient's lungs.
[0018] Reference is now made to
Figures 1A-B which illustrate a schematic view of a nebulizer housing device 1 comprising a
breath actuated mode via mouthpiece or mask interface 2 for covering subject's breathing
system. The nebulizer of the present invention may be an electric- or battery-powered
device that turn liquid medicine into a fine mist that's inhaled into the lungs.
[0019] The present invention provides a nebulizer for dispensing a consecutively dose of
a medicament in the form of a mist, comprising: an energy source (ES) selected from
the group consisting of: LG source, electric motor, electric linear actuator, electromagnetic
solenoid based actuator, spring operated mechanism, hydraulic pump, compressed gas
(CG), flywheel, steam engine, carnot machine, stirling cycle and a combination thereof,
an air-containing volume; an air outlet fluidly connected to the air-containing volume;
an air actuator adapted to release a flow of compressed air through the air outlet
at such time as a predetermined ES pressure has been reached in the volume and at
least two valve means in communication with the air actuator.
[0020] The compressed air is released at a predetermined pressure of about 1.38 to about
6.89 bar (about 20 to about 100 psig). Furthermore, the valve means controls the actuation
of the air actuator such that when a medication is nebulized, a mist distribution
of a medication is formed having droplets size in the range of approximately 1µ to
approximately 7µ which inhaled by a user at a set of predetermined intervals.
[0021] In another embodiment of the present invention, the nebulizer further comprising:
an air actuator comprising at least one inlet of liquefied gas (LG), at least one
air outlet, at least one first LG-expanding volume and at least one second air-containing
volume. The first and second volumes are effectively separated by means of an LG-blocking
member. The nebulizer may further comprise a container with LG source. The container
is in a fluid connection with LG-expanding volume
via at least one LG inlet. The air actuator is facilitating the dose of airflow by allowing
the expansion of the LG in at least one LG-expanding volume from its condensed liquid
phase to its expanded gas phase. Furthermore, the expansion of the LG facilitates
the compression of the air within the at least one air-containing volume, such that
a dose of LG-free air flow is inhalable
via the at least one air outlet. The nebulizer is configured such that when the nebulizer
in use it is positioned at a location to be placed within a patient's oral cavity
and further received in the mouth of a subject.
[0022] The Nebulizer of the present invention may further use LG to break up medical solutions
and suspensions into small aerosol droplets that can be directly inhaled from the
mouthpiece of the device.
[0023] In another embodiment of the present invention, the nebulizer is a portable and handle
hand device and is effective for short and long treatment. Furthermore, the nebulizer
provides an improved lung deposition. The nebulizer is constructed such that the actuator
allows the delivery of a sufficient amount of a compressed air and directs the compressed
air flow in such manner toward the air outlet such that an entire mass of a latter
is released from the nebulizer.
[0024] In another embodiment of the present invention, the LG is preferably Liquefied petroleum
gas, also known as LPG, GPL, LP Gas, liquid petroleum gas or simply propane or butane.
The LPG is a flammable mixture of hydrocarbon gases used as an aerosol propellant.
The LG may be further activated using a valve 12.
[0025] In another embodiment of the present invention, the nebulizer the present invention
may comprise a compressed or pressurized gas.
[0026] The LG is further selected from the group consisting of: 1,1,1,2-tetrafluoroethane
(HFA 134a) or 1,1,1,2,3,3,3-heptafluoropropane (HFA 227) or a mixture thereof. In
alternative propellants such as carbon dioxide or other which are gaseous at room
temperature and standard atmospheric pressure may be used.
[0027] The nebulizer may further comprise a system for delivering a medicament, the system
may comprise an additionally medicament chamber for loading a medicament and a medication
metering valve for releasing the medicament from the chamber. The medication metering
valve is in fluid connection with the medicament chamber. The breath actuated valve
is configured to deliver a specific amount of medicament to the patient's lungs. The
medicament may be delivered in a form of a short burst of aerosolized medication which
is inhaled by the patient.
[0028] Reference are now made to
Figures 2A-C which illustrate an air pressure-operated nebulizer system for spraying a predefined
dose form, comprising: (a) an energy source(ES) such as a liquefied gas (LG) source
11, (b) a volume adapted to contain LG 13a, the volume is fluidly connected to the
LG source 11, (c) an air-containing volume 13b,(d) at least one air outlet fluidly
connected to air-containing volume , (e) actuator means 17 separating the LG-containing
volume from the air-containing volume and, valve means 12 in communication with the
air actuator.
[0029] In another embodiment of the present invention, the air actuator is selected from
a group consisting of a piston pump, a rotor, a turbine, an inflatable membrane, a
spring, and a combination thereof. The actuator may be further integrated with spring
means. The spring means is in communication with the air actuator such that
(i) as a container is filled with LG, the spring is loaded and, (
ii) the dispensing of the air from the container is provided by the application of a
force upon the actuator, by the compressed LG and further by the spring means.
[0030] The spring means may further control the rotation of the actuator. The spring means
is selected from a group consisting of: mechanical spring, gas loaded spring, gas
pressure, or any other method known to one skilled in the art. The spring means may
be configured as a pressurizing recoil which is dependent upon the pressure provided
by the actuator. Once a container is filled with a medication , the spring is loaded,
such that the same is activated, the spring applies pressure upon the actuator so
as to release predetermined amount of the medication in continuously.
[0031] In another embodiment of the present invention, the valve means is synchronized with
subject's breath such that when a medication is nebulized, a mist distribution of
a effective measure of medication is formed having droplets size in the range of approximately
1µ to approximately 7µ which inhaled by a user at a set of predetermined intervals
(e.g, at least one interval may be of at least 1 to 3 minutes). The droplets are released
in a quick succession form at a periodically rate of about 0.1ml to about 3ml droplets
of the medication in less than about 6 minutes. The droplets are preferably released
in a quick succession form at a periodically rate of about 2.5ml droplets of the medication
per approximately 2 minutes.
[0032] Figure 2B further illustrates the nebulizer system comprising valve means designated
herein in a predefined arrangement adjacent to the nebulizer LG inlet having high
pressure LG supplied directly to the valve so that when at least one of valve is opened
in response to system determinations, the gas at high pressure can be substantially
immediately delivered at a steady state of flow and pressure to the nebulizer unit
to nearly or substantially instantaneously begin nebulization producing the proper
distribution range and of particle sizes at a desired density. The valve means further
comprising at least one control valve 12d and at least three directing valves 12a,12b,12c.
The control valve 12d comprises an idle state and an automatic (auto) state for activating
the nebulizer. The directing valves 12a,12b,12c control and further monitor the actuator
movement in the axial direction whilst LG is released by the LG-directing valve 12c
to the LG-expanding volume and further forcing the actuator to downward position .
The directing valves 12b,12a are based upon ferromagnetic mechanism such that when
the actuator is forced to a downward position valve 12b pulls down the actuator and
when the actuator reaches to valve 12a the actuator is released back to its rest position
. The valve means further comprising a medication metering valve 12e which controls
the medication release from the medication container 15 to a nozzles system 16.
[0033] Figure 2C further demonstrates a schematic view of the electric system of the nebulizer further
comprising an energy/propellant source 19 , and a controller 18 for controlling and
activating the breath actuating system, the motor, the medication metering, the counter/timer,
and the valve means in the nebulizer system.
[0034] In another embodiment of the present invention, the actuator means is adapted to
release a flow of compressed air through the air outlet at such time as a predetermined
LG pressure has been reached in the volume adapted to contain LG. The LG and the air
remain separate at all times. Furthermore, the compressed air is released at a predetermined
pressure of about 20 and about 100 psig whilst the LG-expending volume contains a
first compressed LG compressed between about 20 and about 4000 psig. The LG may further
be compressed in a pressure of about 50 to 4000psig. The airflow released from the
nebulizer outlet depended upon differential pressure gauges between the one LG-expanding
volume and the air-containing volume separated by means of an LG-blocking member.
[0035] The LG-expanding volume is adapted for containing a compressed LG at a first pressure.
The air containing volume may be in a selective communication with LG-expanding volume.
The air containing volume is adapted for containing a compressed air at a second pressure
less than the first pressure. Both of the volumes are cooperating so as to yield a
second pressure of the compressed air within the air containing volume. The LG-expanding
volume contains a compressed LG compressed in the range of about 20 to about 200 psig,
and the air containing volume contains compressed air compressed in the range of about
3 to about 10 psig.
[0036] As used herein the term
"about" or
"approximately" denotes ± 25% of the defined amount or measure or value.
[0037] The term
"effective measure" of a medicament refers hereinafter to a medicament dose to be delivered towards patient's
respirator tracks, wherein the dose is sufficient for curing the patient according
to a predefined treatment protocol. It is well within the scope of the invention,
where effective measure ranges from 1 microgram to 1 gram, It is further in the scope
of the invention, where effective measure of the medicaments is provided when characterized
by an average particles size of less than about 5µm. Additional or alternatively,
it is in the scope of the invention, where effective measure of the medicaments is
characterized by a homogeneous medicament, i.e., one or more medicaments introduced
to patient's respiratory tract by air carrier, and not another carrier, such as a
carbon-containing liquefied gas (carbon dioxide, butane, propane etc.). Additional
or alternatively, it is in the scope of the invention, where effective measure of
the medicaments is a minimal dose useful for providing enhanced medicament absorption
and kinetics per internal surface area of patient's alveoli. Additional or alternatively,
it is in the scope of the invention, where effective measure of the medicaments is
characterized by an average particles size (APS) µm, wherein the inhaled medicament
is sized equal or less the APS to absorbed more than 50% per internal surface area
in the alveoli. According to an embodiment of the invention the average particles
size is in a range 0.75 µm≤ APS ≤ 7.0 µm. Furthermore, a differential pressure gauge
is further created between the outlet and inlet ports, each connected to one of the
volume portions whose pressure is to be monitored.
[0038] The term
'medication; medicament; medicine; 'drug', as used herein, refers to any chemical or natural substance formulated or compounded
as single active ingredient or in combination of other pharmacologically active substance,
it may be in a separate but packed in a single unit pack as combination product intended
for internal, or external or for use in medical diagnosis, cure, treatment, prevention
of disease, disorder or to enhance physical or mental well-being. The chemical or
natural substancemay be in a form selected from the group consisting of solid form,
gas form, liquid form and any combination thereof.
[0039] Without wishing to be bound by theory, the size and shape of particles are primordial
factors that condition their deposition in the lungs. The size is defined by the mass
median aerodynamic diameter (MMAD) or diameter of a particle of mass equal to the
average particle diameter of a population, meaning the diameter of a particle in which
50% of the aerosol mass is greater and the other 50% is smaller. Depending on their
size and shape, the particles can be deposited by means of four mechanisms:
Impaction which is a physical phenomenon by which the particles of an aerosol tend to continue
on a trajectory when they travel through the airway, instead of conforming to the
curves of the respiratory tract. Particles with enough momentum (product of the mass
and velocity) are affected by centrifugal force at the points where the airflow suddenly
changes direction, colliding with the airway wall. This mainly happens in the first
10 bronchial generations, where the air speed is high and the flow is turbulent This
phenomenon mainly affects particles larger than 10µm, which are mostly retained in
the oropharyngeal region, especially if the drug is administered by dry powder nebulizers
(DPI) . Interception which is mainly related to fibers, which, due to their elongated
shape, are deposited as soon as they contact the airway wall. Sedimentation which
is a physical phenomenon by which particles with sufficient mass are deposited due
to the force of gravity when they remain in the airway for a sufficient length of
time. This predominates in the last 5 bronchial generations, where the air speed is
slow and the residence time is therefore longer.
Suspension which is a phenomenon by which the particles of an aerosol move erratically from
one place to another in the airways. This happens as a consequence of the Brownian
diffusion of particles with an MMAD smaller than 0.5µm when they reach the alveolar
spaces, where the air speed is practically zero. These particles are generally not
deposited and they are expelled once again upon exhalation. It can generally be considered
that particles with an MMAD higher than 10µm are deposited in the oropharynx, those
measuring between 5 and 10µm in the central airways and those from 0.5 to 5µm in the
small airways and alveoli. Therefore, for topical respiratory treatment it is best
to use particles with an MMAD between 0.5 and 5µm. The nebulizer of the present invention
enables a breathable fraction of a medication mist having a droplets distribution
adjustable between one or more of the following rangers: 0.5-7.5 µm, 0.5-2.5 µm, 2.5-5.0
µm or 5.0-7.5µm.
[0040] In another embodiment of the present invention, the deposition of fluid particles
of the nebulizer of the present invention is proportional to the inspiratory flow.
This is due to the fact that the increased inspiratory flow reduces the residence
time of the particles in the airway, therefore the effects of the severity and of
the Brownian movement will be quite lower. A minimal inspiratory flow is necessary
to drag the particles toward the interior of the bronchial tree.
[0041] In another embodiment of the present invention, the nebulizer of the present invention
further comprises inlets and outlets having an optimize diameter which allow correlation
between droplets size medication dose and further droplets distribution in a predefined
velocity and time.
[0042] According to one embodiment of the present invention, the nebulizer system comprises
a medication container. The medication is selected from the group consisting of granular
matter, a drug sized to form fine particles, powder, sol, gel, sol-gel, glass, encapsulated
matter, milled composition or any combination thereof. Alternatively or additionally,
the medicament may be utilized in a liquid phase. In such a case, the fluid is selected
in a non-limiting manner from water miscible compositions, water immiscible compositions,
emulsions, extracts, dispersions, suspensions, vasiculated solutions, aggregated phases
or any combination thereof. It is according to another embodiment of the present invention
wherein the fluid or medicament is selected in a non-limiting manner from at least
one of the group of Braochodilators, especially sympatic mimetics, alfa antagonists,
anti cholinergics; nasal decongestants, such as pseudoehedrines, ephedrines; steroids;
anti histamines; anti prostaglandins, alternative or homeopathic medicaments; vaso
constrictors; local anesthetics; mast cell stabilizers; antibiotics, such as biocides,
fungicides etc; pleasant odor; pheromones; hormone treatments, such as ADH, insulin,
growth hormones; vapors, humidifiers; drying compositions; hot or cold vapors; hyper-,
iso- or hypotonic vapors or any combination thereof, or decongestants, essential oils,
volatile compounds, etheric oils, terepenes, terpanols and either water miscible or
water-immiscible extracts, especially oils or extracts .
[0043] In another embodiment the nebulizer may further be adapted for treating asthma, chronic
obstructive pulmonary disease (COPD) and other respiratory diseases and conditions.
The medicament may be in a form selected from the group consisting of solid form,
gas form, liquid form and any combination thereof.
[0044] According to one embodiment of the present invention, the nebulizer is further configured
to deliver a medicament for treating chronic inflammatory diseases such as asthma,
as presented in
Table 1 below:
TABLE 1
Medicament types |
Purpose |
Category |
Inhaled corticosteroids |
Taken regularly to control chronic symptoms and prevent asthma attacks - the most
important type of treatment for most people with asthma |
Long-term asthma control medicaments |
Leukotriene modifiers |
Long-acting beta agonists (LABAs) |
Theophylline |
Combination nebulizers that contain both a corticosteroid and a LABA |
Short-acting beta agonists such as albuterol |
Taken as needed for rapid, short-term relief of symptoms - used to prevent or treat
an asthma attack |
Quick-relief medicaments (rescue medicaments) |
Ipratropium (Atrovent) |
Oral and intravenous corticosteroids (for serious asthma attacks) |
Allergy shots (immunotherapy) |
Taken regularly or as needed to reduce your body's sensitivity to a particular allergy-causing
substance (allergen) |
Medicaments for allergy-induced asthma |
Omalizumab (Xolair) |
[0045] Other medicaments may further be adapted , selected from the group consisting of:
Bronchodilators Short-acting bronchodilators (including: Anticholinergics (such as
ipratropium),Beta2-agonists (such as albuterol and levalbuterol)), a combination of
the two Long-acting bronchodilators, (including: Anticholinergics (such as tiotropium),Beta2-agonists
(such as salmeterol, formoterol, and arformoterol)),Phosphodiesterase-4 (PDE4) inhibitors,
Corticosteroids (such as prednisone), Expectorants, (such as guaifenesin (Mucinex)),
Methylxanthines.
[0046] Other medicaments may further be adapted for treating Chronic obstructive pulmonary
disease (COPD), selected from the group consisting of: Aclidinium inhalation, aclidinium/formoterol
inhalation, AM211, AZD1981(CRTh2 receptor antagonist), AZD 2115 (MABA), AZD2423 (CCR2b
antagonist), AZD3199(iLABA), AZD5069(CXCR2), AZD5423, AZD3199, AZD5069(CXCR2), AZD5423
(inhaled SEGRA), AZD8683(muscarinic antagonist), BCT197, BI-137882, BIO-11006, Dulera
mometasone/formoterol, EP-101(LAMA), EP-102(LAMA/LABA), EPI-12323, formoterol/ fluticasone
fixed-dose combination(inhalation), GSK256066(inhaled PDE4 inhibitor), GSK573719(muscarinic
acetylcholine antagonist), GSK573719/ vilanterol (muscarinic acetylcholine antagonist/long-acting
beta2 agonist), GSK610677 (inhaled p38 kinase inhibitor), GSK961081(muscarinic antagonist/beta2
agonist), GSK1325756(chemokine receptorantagonist-2), GSK2245840
(SIRT1 activator), Ilaris canakinumab, LAS 100977(LABA), levosalbutamol /ipratropiuminhalation
solution, losmapimod(oral p38 kinase inhibitor), MEDI-2338(anti-IL-18 mAb), MEDI-8968(anti-IL-1R),
MK-7123(navarixin), MN-166(ibudilast), MN-221(bedoradrine), NVA237
(glycopyrrolate inhalation), O-desulfated heparin intravenous, olodaterol, olodaterol/tiotropium
bromide, paclitaxel-loaded stent, PF-03715455, PH-797804, Prochymal remestemcel-L,
PT001(glycopyrrolate inhalationaerosol), PT003(glycopyrrolate/formoterol inhalation
aerosol), PT005(formoterol inhalation aerosol), PUR118, QMF149 (indacaterol/mometasone),
QVA149(glycopyrrolate/indacaterol inhalation), Relovair vilanterol/fluticasone furoate,
RV568, TD-4208(LAMA), tetomilast, vilanterol(long-acting beta2 agonist), Veldona interferon-alpha,
and a combination thereof.
[0047] In another embodiment of the present invention, the nebulizer may be adapted for
topical administration or for systemic absorption of drugs delivered for the local
treatment of respiratory disease. The nebulizer is further efficient and reproducible
systemic delivery is lung deposition.
[0048] In another embodiment of the present invention, the nebulizer may be used with therapeutic
agents that are antiasthmatics, including bronchodilators and antiinflammatories,
particularly of steroid type, having a local therapeutic action in the lungs and/or
a systemic therapeutic action after absorption in the blood.
[0049] The nebulizer of the present invention are also suitable for dispensing any medicaments
which may be administered in aerosol formulations and useful in inhalation therapy
e.g.; anti-allergics, e.g. cromoglycate (e.g. as the sodium salt), ketotifen or nedocromil
(e.g. as sodium salt); anti-inflammatory steroids, e.g. beclomethasone (e.g. as dipropionate),
fluticasone (e.g. flunisolide, budesonide, rofleponide, mometasone (e.g as furoate),
ciclesonide, triamcinolone acetonide; anticholinergics, e.g. ipratropium (e.g. as
bromide), tiotropium, atropine or oxitropium and salts thereof. It will be clear to
a person skilled in the art that, where appropriate, the medicaments may be used in
the form of salts, (e.g. as alkali metal or amine salts or as acid addition salts)
or as esters (e.g. lower alkyl esters) or as solvates (e.g. hydrates) to optimize
the activity and/or stability of the medicament and/or to minimise the solubility
of the medicament in the propellant. Medicament may be used in the form of racemate
or in the form of a pure isomer e.g. R-salmeterol or S-salmeterol.
[0050] In another embodiment of the present invention the nebulizer may further comprise
monitoring system such as a sensor which detects and may further control the rotation
of the actuating member in order to count the actuations of the nebulizer. The sensor
is further adapted for breath actuating mechanism such that when the fluid, preferably
a liquid, more particularly a pharmaceutical composition such as medication , is nebulized,
an aerosol is formed that can be breathed in or inhaled by a user. Usually the inhaling
is done at least once a day, more particularly several times a day, preferably at
set intervals.
[0051] In another embodiment of the present invention, the sensor may be an air flow sensor
positioned within the air-containing volume and configured to generate signals indicative
of air flow generated by a patient's involuntary cough event occurring at nebulization
and further a processor configured to receive signals from the air flow sensor and
to evaluate the involuntary cough event. The sensor may further send a feedback signal
to adjust and vary the amount of resistance to the air flow for respiratory exercise
training and incentive spirometry use. Pressure sensor may further be used to indirectly
measure other variables such as fluid/gas flow, speed, water level, and altitude.
The pressure sensor is selected from the group consisting of gauge pressure sensor,
differential pressure sensor, absolute pressure sensor, sealed pressure sensor and
any combination thereof.
[0052] In another embodiment of the present invention, the monitoring elements may further
count the actuations of the nebulizer by detecting any rotation of the inner part
relative to the upper part of the housing. The monitoring device may further operate
purely or partially mechanically.
[0053] Reference is now made to
Figures 3A-B which illustrate a nozzles system 100 of the present invention for dispensing an
effective measure of a medicament in the form of a mist, comprising: a nebulizer comprising
an air actuator comprising at least one inlet of liquefied gas (LG), at least one
air outlet, at least one first LG-expending volume and at least one second air-containing
volume, the first and second volumes are effectively separated by means of an LG-blocking
member, a container with a LG source. The container is in a fluid connection with
the LG-expending volume
via at least one LG inlet , valve means in communication with the air actuator and at
least two nozzles in fluid communication with the nebulizer's air outlet.
[0054] Figure 3A further illustrates a classic venturi nozzles system 100 comprising an air inlet
120, a medication inlet 110 and a medication- air mixture outlet 130. The venturi
nozzles system is designated for the medication rate of flow comparing to the air
rate of flow and further for decrease the medication droplet size or medication particle
size. The medication particle size dispersed from the nebulizer of the present invention
is proportional to the air velocity due to the shear forces and surface tension balance
on each droplet.
[0055] Figure 3B further illustrates a cross section of the nebulizer of the present invention comprising
venturi nozzles in a predefined arrangement. The venturi nozzle is based upon a push
and pulls mechanism. The nebulizer comprises an air inlet 160 for delivering air flow
, a medication inlet 170 ,a medication reservoir 150 and an air-medication mixture
outlet 140 for delivering the fluid or medication droplets. The air inlet diameter
is configured to provide a pressure difference such that the downstream pressure may
further empty the inner cavity of the liquid reservoir and prevent unnecessary residuals
resulting from low pressure or any fluid adherent within the nebulizer. The venturi
nozzle, low pressure mixing chamber and the air-containing volume are configured such
that at standard temperature and pressure (STP) a differential pressure results in
no medication that is drawn upward through the primary suction line for nebulization
and discharged through the nebulizer outlet until a negative inspiratory pressure
is created from inhalation by the subject. Furthermore, the venturi nozzle may be
horizontally oriented when in use.
[0056] It is another embodiment of the present invention, at least one nozzle is configured
with a diameter of about 0.2mm to about 0.9mm to provide a droplets distribution of
more than 70% of a medication.
[0057] It is another embodiment of the present invention, at least one nozzle is preferably
with a diameter of about 0.5mm to disperse a droplets size is in a range of about
2µ to about 3µ.
[0058] It is another embodiment of the present invention, at least one first nozzle is preferably
with a diameter of about 0.3mm and at least one second nozzle is with a diameter of
about 0.5mm, respectively.
[0059] Preferably, the overall cross sectional area of the nozzle outlets is 25 to 500 square
micrometers.
[0060] As
Figure 3B demonstrates, the air within the air inlet flow via constricted section with a reduced
diameter, the reduction in diameter causes an increase in the fluid flow speed thus
the velocity of the fluid increases as the cross sectional area decreases, with the
static pressure correspondingly decreasing resulting a fluid suction. Thereby ,an
increase in the speed of the fluid occurs simultaneously with a decrease in pressure
or a decrease in the fluid's potential energy (e.g Venturi effect).Furthermore, when
the fluid such as a medication, flows through the nozzle tube that narrows to a smaller
diameter, the partial restriction causes a higher pressure at the inlet than that
at the narrow end. This pressure difference causes the fluid to accelerate toward
the low pressure narrow section, in which it thus maintains a higher speed. The direct
relationship between pressure difference and fluid speeds may further allow to determine
the volumetric flow rate.
[0061] In another embodiment of the present invention, in order to provide a negative pressure,
thus sucking in all of the fluid, the liquid reservoir is further connected to an
additional narrow tube which further configured to provide additional pressure from
the back side of the liquid reservoir. The additional pressure enables and accelerates
the reservoir emptying from the remained liquid droplets.
[0062] The venturi nozzles system is designated for the medication rate of flow comparing
to the air rate of flow and further for decreasing the medication droplet size or
medication particle size. The medication particle size dispersed from the nozzles
system of the present invention is proportional to the air velocity due to the shear
forces and surface tension balance on each droplet.
[0063] The formulation below demonstrates the calculation of flow rate using orifice plate
calculator for incompressible flow, based on the Bernoulli principle:
where is:
p - pressure
ρ - density
V - velocity
g - gravitational constant (9.81 m/s2)
z - geodetic height
when assuming that the pressure lost is negligible (pressure drop is obvious and included
with coefficient of discharge as introduced bellow):
and:
[0064] When velocities substituted with flow rate:
where is: Q - volumetric flow rate
D - diameter
[0065] Pressure drop through the orifice resulting from the increase of velocity which may
be calculated as follows:
or:
[0066] Expressing flow rate from the previous equation leads to:
[0067] Substituting:
[0068] Additional values are calculated using following equations:
Mass flow:
Velocities:
[0069] Referring to Bernoulli's equation in the special case of incompressible flows, the
theoretical pressure drop at the constriction is given by:
where
ρ is the density of the fluid, υ
1 is the (slower) fluid velocity where the pipe is wider, υ
2 is the (faster) fluid velocity where the pipe is narrower (as seen in the figure).
This assumes the flowing fluid (or other substance) is not significantly compressible
- even though pressure varies, the density is assumed to remain approximately constant.
[0070] A venturi may be further used to measure the volumetric flow rate,
Q.
[0071] Since
then
[0072] The nebulizer is configured to increase both (
i) deposition of a medicament and (
ii) kinetics per internal surface area of the alveoli to the respiratory tract by means
of a dual nozzles system.
[0073] In another embodiment of the present invention, the nozzles system of the present
invention may comprise at least one venturi nozzle thus, based upon venturi effect
as a jet effect. The velocity of the fluid increases as the cross sectional area decreases,
with the static pressure correspondingly decreasing.
[0074] In another embodiment of the present invention the nozzles system of the present
invention may comprise at least one Laskin nozzle or/and swirl nozzle interconnected
with a venturi nozzle in a predefined direction and angle.
[0075] In another embodiment of the present invention, the nozzles system may comprise at
least two venturi nozzles interconnected in a predetermined angle (α,β) and direction
such that the droplet size of a medication dispersed from the nebulizer is in a range
of about 1µm to about 5µm. The nozzle-system further provides jets of liquid which
converge at an optimized angle therefore, dispersing an effective measure of medication
having an average particles size in the range of about 1µm to about 7µm.
[0076] In another embodiment of the present invention, the air outlet may further include
an orifice having a diameter of about 0.5mm to about 1.5mm, operably configured to
emit effective measure of the medicament having average particles size equal to or
less than 5µm. Additional or alternatively, the LG is with a pressure operably configured
to emit effective measure of the medicament having average particles size equal to
or less than 5µm. Additional or alternatively, the second air-containing volume is
with a volume operably configured to emit effective measure of the medicament having
average particles size equal to or less than 5µm. Additional or alternatively, the
actuator is with a speed of movement operably configured to emit high medicament quantity
having average particles size equal to or less than 5µm.
[0077] Reference is now made to
Figures 4A-B which illustrate the nozzles system of the present invention, comprising a dual
nozzle arrangement configured in a predefined angle (α, β<90°) on which a primary
air stream accelerates the medication flow. The nozzles system comprises a primary
orifice 220, a secondary orifice 230 and further an exit orifice which designated
to provide a preretirement droplet size of a medication dispersed from the nozzles
system having a diameter in a range of about 1µm to about 5µm.
[0078] Without wishing to be bound by theory, according to the laws governing fluid dynamics,
a fluid's velocity must increase as it passes through a constriction to satisfy the
principle of continuity, while its pressure must
decrease to satisfy the principle of conservation of mechanical energy. Thus, any gain in
kinetic energy a fluid may accrue due to its increased velocity through a constriction
is negated by a drop in pressure.
[0079] In the nebulizer of the present invention the medication flows through a nozzle comprising
a tube that narrows to a smaller diameter thus, the partial restriction causes a higher
pressure at the inlet than that at the narrow end. This pressure difference causes
the medication to accelerate toward the low pressure narrow section, in which it thus
maintains a higher speed. The venturi nozzles system of the present invention uses
the direct relationship between pressure difference and fluid speeds to determine
the volumetric flow rate of a medication and further to provide medication droplets
size in the range of about 0.75 µ to 7µ. An equation for the drop in pressure due
to the Venturi effect may be derived from a combination of Bernoulli's principle and
the continuity equation.
[0080] In another embodiment of the present invention, at least two nozzles are interconnected
in a vertically or horizontally manner to each other.
[0081] In another embodiment of the present invention, the nebulizer meets and compliance
with FDA regulations.
[0082] Reference is now made to
Figures 5A-5D which illustrate a colliding stream nozzles system predefined arrangement. The colliding
stream nozzles system comprises a first air channel 310, a second air channel 320,
and a medication channel 330. When a medication is released from the medication channel
330 a mixture of air and medication is obtained within the mix channel 340 resulting
a droplets size in a predefined velocity and rate.
Figure 5C further illustrates that a mixture of medication and air in a predefined velocity
already obtained.
[0083] Figure 5D further illustrates the incompressible flow, based on the Bernoulli principle between
port 1 to port 7:
[0084] Where:
P - pressure
ρ - density
V - velocity
g - gravitational constant (9.81 m/s2)
z - geodetic height
H - Head losses
[0087] The sum of energy losses is the energy required to refraction of the liquid into
small droplets.
[0088] Continuity equation:
ρ
GL - average density of Gas and liquid
[0089] Examples
[0090] Symmetric distribution
[0091] From continuity equation:
[0092] The average density is function of the volume, therefore:
And
ĖSum ≈ 34
W
[0093] As demonstrates above the droplets size is controlled and changed resulting from
the different diameters thereby different velocities. Table 2 below demonstrated the
the diameter of ports 2, 3 and 4, the droplets velocity and droplets size derived.
TABLE 2
Diameter of droplets (µm) |
V4 (m/s) |
V3 (m/s) |
D4 (mm) |
D3 (mm) |
V2 (m/s) |
D2 (mm) |
|
2 |
254 |
254 |
0.5 |
0.5 |
75 |
1.0 |
I |
4 |
176 |
176 |
0.6 |
0.6 |
75 |
1.0 |
II |
6 |
99 |
99 |
0.8 |
0.8 |
75 |
1.0 |
III |
[0094] The embodiments were chosen and described to provide the best illustration of the
principals of the invention and its practical application, and to enable one of ordinary
skill in the art to utilize the invention in various embodiments and with various
modifications as are suited to the particular use contemplated. All such modifications
and variations are within the scope of the invention as determined by the appended
claims when interpreted in accordance with the breadth they are fairly, legally, and
equitably entitled.
[0095] Reference is now made to
Figures 6 to 19 which illustrate graphs of droplets distribution which determine the quality of the
mist sprayed out of the present invention's custom designed nozzles system.
[0096] Figure 16 further demonstrates a Gaussian curve of the droplets diameter of a medication dispersed
from the nebulizer comprising the nozzles system of the present invention vs. the
particles percentage amount. As illustrated, the nebulizer may provide more that 50%
droplets from the medication droplets population having a 2mµ diameter. Furthermore,
the nebulizer may further provide more than 75% droplets from the medication droplets
population having a 3mµ diameter. The graph is characterized by a bell-shaped curve
of the diffusion of medication particles which further illustrates that an optimal
absorption percentage of medication can be achieved in droplets size in the range
of about 0.8µ to about 6µ.
[0097] The nebulizer was further tested using the MALVERN Spray tech particle sizing analyzer
for determining the droplets diameter and duration vs. the medication dispersed dose.
[0098] Table 3 below demonstrates the particle size and distribution when using the nebulizer
of the present invention. The nebulizer of the present invention is with ability to
generate a mist that consists of 80% droplets smaller than 3 microns and 90% droplets
smaller than 5 microns.
TABLE 3
Accumulated distribuition> 80% range[µ] |
Accumulated distribuition >75% range [µ] |
Peak particle size [µ] |
CRITERIA\NOZZLE EXP |
2.154-2.512 |
1.848-2.154 |
∼1.8 |
1_3.5b_27mms_C |
2.154-2.512 |
1.848-2.154 |
∼2.0 |
1_3.5b_27mms_D |
2.154-2.512 |
1.848-2.154 |
∼2.0 |
Summary 3.5bar |
2.512-2.929 |
2.154-2.512 |
∼1.5 |
1_4b_27mms_3 |
2.512-2.929 |
2.154-2.512 |
∼1.4 |
1_4b_27mms_4 |
2.512-2.929 |
2.154-2.512 |
∼1.5 |
Summary 4 bar |
7.356-8.577 |
7.356-8.577 |
∼4.3 |
DBL_3.2B_1 |
the present invention further provides a nebulizer for improving medicament's alveolar
deposition is with a medication lunching velocity of about 40µL/s, air velocity of
about 100cc/s, whilst the minimum diameter of the tube of the venturi system is of
about 0.95mm and the minimum diameter of the medication inlet is of about 0.38mm.
This results an air-medication mixture having a velocity of about 20m/s. The nebulizer
further provides droplets with an average diameter of about 2.4µ.
[0099] In another embodiment of the present invention, the nebulizer may further be adapted
for systemic administration of active compounds and drug compositions (e.g via a route
of administration of medication nutrition or other substance into the circulatory
system so that the entire respiratory system is affected), therefore, adapting the
pulmonary rout or the respiratory system as a port of entry for systemic distribution
and/or absorption of drugs (e.g. insulin) via enteral administration.
1. A nebulizer (1) for dispensing a dose of a medicament in the form of a mist, the nebulizer
comprising:
a. an energy source (ES) (11);
b. an air-containing volume (13b);
c. an air outlet fluidly connected to said air-containing volume;
d. an air actuator (17) in communication with at least two valve means, the air actuator
being adapted to release a flow of compressed air, at a predetermined pressure of
about 1.38 to about 6.89 bar (about 20 to about 100 psig), from the air-containing
volume through said air outlet by application of force from the energy source (ES)
at such time as a predetermined pressure has been reached in said air-containing volume;
and
e. a nozzle system (16) fluidly connected to said air outlet to receive said flow
of compressed air and being adapted to provide a predetermined distribution of the
medicament mist dispensed from the nebulizer;
the nebulizer being characterized in that said nozzle system comprises a medication inlet (240 ; 330), and a dual nozzle arrangement
comprising first and second nozzles (220, 230; 310, 320) interconnected with a predetermined
angle (α) and direction and being configured to provide first and second colliding
streams creating said medicament mist, wherein said first stream is an air stream
flowing in said first nozzle and said second stream flowing in said second nozzle
is either an air stream wherein said medication inlet is located at the intersection
between the first and second nozzles, or a mist stream wherein said medication inlet
is in fluid communication with the second nozzle.
2. The nebulizer according to claim 1, wherein said energy source (ES) (11) comprises
at least one of the following: Liquefied gas (LG) source, electric motor, electric
linear actuator, electromagnetic solenoid based actuator, spring operated mechanism,
hydraulic pump, compressed gas (CG), flywheel, steam engine, carnot machine, and stirling
cycle.
3. The nebulizer according to claim 2, wherein said energy source (ES) (11) comprises
the liquefied gas (LG) source, the system further comprising a liquefied gas (LG)
outlet and a liquefied gas (LG) containing volume (13a) fluidly connected to the liquefied
gas (LG) source and being adapted to contain liquefied gas (LG).
4. The nebulizer according to any one of the preceding claims, wherein said at least
two valve means has at least one of the following configurations: (a) it comprises
at least one control valve (12d) having an idle state and an automatic state and at
least two directing valves (12a, 12b) configured to identify and control movement,
position and direction of said air actuator, and (b) it comprises an energy source
(ES) valve (12c) in a fluid connection with said energy source (ES) being configured
to control movement of said air actuator.
5. The nebulizer according to claim 4, wherein said valve means (12) is configured to
release said medication mist in a quick succession form at a periodically rate of
about 2.5ml droplets of said medication per 2 minutes.
6. The nebulizer according to any one of the preceding claims, wherein said air actuator
(17) has at least one of the following configurations: (a) said air actuator is partially
composed of ferromagnetic material; and (b) said air actuator comprises at least one
of the following: a piston pump, a turbine, a rotor, and an inflatable membrane spring.
7. The nebulizer according to any one of claims 3 to 6, wherein said energy source (ES)
(11) comprises the liquefied gas (LG) source and wherein said air actuator (17) is
separating said liquefied gas (LG) containing volume (13a) from said air-containing
volume (13b); said air actuator is facilitating said dose airflow by allowing the
expansion of said liquefied gas (LG) in said at least one liquefied gas (LG)-containing
volume from its condensed liquid phase to its expanded gas phase.
8. The nebulizer according to any one of the preceding claims, wherein said nozzle system
(16) comprises at least one of the following nozzle types: venturi nozzle, laskin
nozzle, annular flow high velocity, additive energy nozzles, and swirl nozzle.
9. The nebulizer according to any one of the preceding claims, wherein said predetermined
angle is one of the following: a) smaller than 90°, and b) equal to 180°.
10. The nebulizer according to any one of the preceding claims, configured for spraying
the medicament comprising one or more of the following: gas materials, liquid materials,
fine particles, powder materials.
11. The nebulizer according to any one of the preceding claims, configured for being activated
manually, semi manually or electrically.
12. The nebulizer according to any one of the preceding claims, additionally comprising
at least one of the following: (a) a medicament metering mechanism comprising a medicament
chamber (15) and metering valve (12e); said metering valve is in fluid connection
with said medicament chamber, (b) a power source comprising at least one of the following:
a battery, an electric source, a rechargeable battery, an electric motor, (c) a breath
actuation means which responds to inhalation by a subject when it senses subject's
breath; (d) a breath actuation means configured to sense negative pressure of patient
inhalation and using that sensing to trigger or initiate high pressure gas flow, said
breath actuation means comprising at least one of a pressure sensor, and Intake Air
Temperature (IAT) sensor, and (e) a spring means in communication with said air actuator,
said spring means comprising at least one of mechanical spring, gas loaded spring,
and gas pressure.
13. The nebulizer according to claim 12, wherein said energy source (ES) (11) is a liquefied
gas (LG) source comprising liquefied petroleum gas (LPG), said spring means being
in communication with said air actuator such that (i) as the liquefied gas (LG) container
is filled with said liquefied petroleum gas (LPG), said spring is loaded; and, (ii) the dispensing of said medication is provided by the application of force upon said
actuator, by means of said spring with said liquefied petroleum gas (LPG).
14. The nebulizer according to any one of the preceding claims, wherein said medication
is a liquid and said first and second nozzles (220, 230; 310, 320) and medication
inlet (240 ; 330) have dimensions providing the dispensed medication mist having medication
droplets of the size between 1µm to 7µm.
1. Vernebler (1) zum Abgeben einer Dosis eines Arzneimittels in der Form eines Nebels,
wobei der Vernebler Folgendes umfasst:
a. eine Energiequelle (energy source - ES) (11);
b. ein Luft enthaltendes Volumen (13b);
c. einen Luftauslass, der mit dem Luft enthaltenden Volumen fluidverbunden ist;
d. einen Luftstellantrieb (17), der mit wenigstens zwei Ventilmitteln in Kommunikation
steht, wobei der Luftstellantrieb geeignet ist, um eine Pressluftströmung bei einem
vorgegebenen Druck von etwa 1,38 bis etwa 6,89 bar (etwa 20 bis etwa 100 psig) aus
dem Luft enthaltenden Volumen durch den Luftauslass durch Aufbringung von Kraft aus
der Energiequelle (ES) zu einem derartigen Zeitpunkt freizusetzen, an dem ein vorgegebener
Druck in dem Luft enthaltenden Volumen erreicht wurde; und
e. ein Düsensystem (16), das mit dem Luftauslass fluidverbunden ist, um die Pressluftströmung
aufzunehmen, und das geeignet ist, um eine vorgegebene Verteilung des Arzneimittelnebels,
der aus dem Vernebler abgegeben wird, bereitzustellen;
wobei der Vernebler dadurch gekennzeichnet ist, dass das Düsensystem einen Medikationseinlass (240; 330) und eine Doppeldüsenanordnung
umfasst, die eine erste und eine zweite Düse (220, 230; 310, 320) umfasst, die mit
einem/einer vorgegebenen Winkel (α) und Richtung miteinander verbunden sind und konfiguriert
sind, um einen ersten und einen zweiten kollidierenden Strom bereitzustellen, die
den Arzneimittelnebel erzeugen, wobei der erste Strom ein Luftstrom ist, der in der
ersten Düse strömt, und der zweite Strom, der in der zweiten Düse strömt, entweder
ein Luftstrom, wobei sich der Medikationseinlass an der Schnittstelle zwischen der
ersten und der zweiten Düse befindet, oder ein Nebelstrom, wobei der Medikationseinlass
in Fluidkommunikation mit der zweiten Düse steht, ist.
2. Vernebler nach Anspruch 1, wobei die Energiequelle (ES) (11) Folgendes umfasst:
eine Flüssiggas(liquefied gas - LG)quelle, einen Elektromotor, einen elektrischen Linearstellantrieb, einen auf
elektromagnetischem Solenoid basierenden Stellantrieb,
einen federbetriebenen Mechanismus, eine Hydraulikpumpe, ein Pressgas (compressed gas - CG), ein Schwungrad, eine Dampfmaschine, eine Carnotmaschine und/oder einen Stirling-Prozess.
3. Vernebler nach Anspruch 2, wobei die Energiequelle (ES) (11) die Flüssiggas(LG)quelle
umfasst, wobei das System ferner einen Flüssiggas(LG)auslass und ein Flüssiggas (LG)
enthaltendes Volumen (13a) umfasst, das mit der Flüssiggas(LG)quelle fluidverbunden
ist und geeignet ist, um Flüssiggas (LG) zu enthalten.
4. Vernebler nach einem der vorhergehenden Ansprüche, wobei die wenigstens zwei Ventilmittel
folgende Konfigurationen aufweisen:
(a) es umfasst wenigstens ein Steuerventil (12d) mit einem Ruhezustand und einem automatischen
Zustand und wenigstens zwei Leitventile (12a, 12b), die konfiguriert sind, um Bewegung,
Position und Richtung des Luftstellantriebs zu identifizieren und zu steuern, und/oder
(b) es umfasst ein Energiequellen(ES)ventil (12c) in einer Fluidverbindung mit der
Energiequelle (ES), das konfiguriert ist, um die Bewegung des Luftstellantriebs zu
steuern.
5. Vernebler nach Anspruch 4, wobei das Ventilmittel (12) konfiguriert ist, um den Medikationsnebel
in einer schnellen Folgeform bei einer periodischen Rate von etwa 2,5 ml Tröpfchen
der Medikation pro 2 Minuten freizusetzen.
6. Vernebler nach einem der vorhergehenden Ansprüche, wobei der Luftstellantrieb (17)
folgende Konfigurationen aufweist:
(a) der Luftstellantrieb besteht teilweise aus ferromagnetischem Material; und/oder
(b) der Luftstellantrieb umfasst Folgendes:
eine Kolbenpumpe, eine Turbine, einen Rotor und/oder eine aufblasbare Membranfeder.
7. Vernebler nach einem der Ansprüche 3 bis 6, wobei die Energiequelle (ES) (11) die
Flüssiggas(LG)quelle umfasst und wobei der Luftstellantrieb (17) das Flüssiggas (LG)
enthaltende Volumen (13a) von dem Luft enthaltenden Volumen (13b) trennt;
wobei der Luftstellantrieb die Dosisluftströmung durch Ermöglichen der Expansion des
Flüssiggases (LG) in dem wenigstens einen Flüssiggas (LG) enthaltenden Volumen von
seiner kondensierten flüssigen Phase in seine expandierte Gasphase erleichtert.
8. Vernebler nach einem der vorhergehenden Ansprüche, wobei das Düsensystem (16) die
folgenden Düsenarten umfasst:
eine Venturidüse, eine Laskindüse, ringförmige hohe Strömungsgeschwindigkeit,
Zusatzenergiedüsen und/oder eine Dralldüse.
9. Vernebler nach einem der vorhergehenden Ansprüche, wobei der vorgegebene Winkel Folgendes
ist:
a) kleiner als 90° oder
b) gleich 180°.
10. Vernebler nach einem der vorhergehenden Ansprüche, der zum Sprühen des Arzneimittels
konfiguriert ist, das eines oder mehrere der Folgenden umfasst: Gasmaterialien, flüssige
Materialien, feine Partikel, Pulvermaterialien.
11. Vernebler nach einem der vorhergehenden Ansprüche, der zum manuellen, halbmanuellen
oder elektrischen Aktivieren konfiguriert ist.
12. Vernebler nach einem der vorhergehenden Ansprüche, der zusätzlich Folgendes umfasst:
(a) einen Arzneimitteldosierungsmechanismus, der eine Arzneimittelkammer (15) und
ein Dosierungsventil (12e) umfasst;
wobei das Dosierungsventil in Fluidverbindung mit der Arzneimittelkammer steht,
(b) eine Leistungsquelle, die Folgendes umfasst:
eine Batterie, eine elektrische Quelle, eine wiederaufladbare Batterie, einen Elektromotor,
(c) ein Atembetätigungsmittel, das auf eine Inhalation eines Subjekts reagiert, wenn
es einen Atem des Subjekts erfasst;
(d) ein Atembetätigungsmittel, das konfiguriert ist, um einen Unterdruck der Inhalation
eines Patienten zu erfassen und dieses Erfassen zu verwenden, um eine Hochdruckgasströmung
auszulösen oder einzuleiten, wobei das Atembetätigungsmittel einen Drucksensor und/oder
einen Ansauglufttemperatur(Intake Air Temperature - IAT)sensor umfasst, und/oder (e) ein Federmittel, das in Kommunikation mit dem Luftstellantrieb
steht, wobei das Federmittel eine mechanische Feder, eine gasbelastete Feder und/oder
einen Gasdruck umfasst.
13. Vernebler nach Anspruch 12, wobei die Energiequelle (ES) (11) eine Flüssiggas(LG)quelle
ist, die flüssiges Propangas (
liquefied petroleum gas - LPG) umfasst, wobei das Federmittel mit dem Luftstellantrieb derart in Kommunikation
steht, dass
(i) wenn der Flüssiggas(LG)behälter mit dem flüssigen Propangas (LPG) gefüllt wird, die
Feder belastet wird; und
(ii) das Abgeben der Medikation durch die Aufbringung von Kraft auf den Stellantrieb mittels
der Feder mit dem Flüssiggas (LPG) bereitgestellt wird.
14. Vernebler nach einem der vorhergehenden Ansprüche, wobei die Medikation eine Flüssigkeit
ist und die erste und zweite Düse (220, 230; 310, 320) und der Medikationseinlass
(240; 330) Abmessungen aufweisen, die den abgegebenen Medikationsnebel mit Medikationströpfchen
der Größe zwischen 1 µm bis 7 µm bereitstellen.
1. Nébuliseur (1) permettant l'administration d'une dose d'un médicament sous forme de
brume, le nébuliseur comprenant :
a. une source d'énergie (ES) (11) ;
b. un volume contenant de l'air (13b) ;
c. une sortie d'air raccordée fluidiquement audit volume contenant de l'air ;
d. un actionneur pneumatique (17) en communication avec un moyen formant au moins
deux soupapes, l'actionneur pneumatique étant conçu pour libérer un écoulement d'air
comprimé, à une pression prédéterminée d'environ 1,38 à environ 6,89 bar (environ
20 à environ 100 psig), à partir du volume contenant de l'air à travers ladite sortie
d'air par application d'une force provenant de la source d'énergie (ES) lorsqu'une
pression prédéterminée a été atteinte dans ledit volume contenant de l'air ; et
e. un système de buses (16) raccordé fluidiquement à ladite sortie d'air de manière
à recevoir ledit écoulement d'air comprimé et étant conçu pour fournir une distribution
prédéterminée de la brume de médicament administrée à partir du nébuliseur ;
le nébuliseur étant caractérisé en ce que ledit système de buses comprend une entrée de médicament (240 ; 330), et un agencement
à deux buses comprenant des première et seconde buses (220, 230 ; 310, 320) raccordées
par un angle (α) et une direction prédéterminés et étant conçues pour fournir des
premier et second courants entrant en collision pour créer ladite brume de médicament,
ledit premier courant étant un courant d'air s'écoulant dans ladite première buse
et ledit second courant s'écoulant dans ladite seconde buse étant soit un courant
d'air, ladite entrée de médicament étant située à l'intersection entre les première
et seconde buses, ou un courant de brume, ladite entrée de médicament étant en communication
fluidique avec la seconde buse.
2. Nébuliseur selon la revendication 1, dans lequel ladite source d'énergie (ES) (11)
comprend : une source de gaz liquéfié (LG), et/ou un moteur électrique, et/ou un actionneur
linéaire électrique, et/ou un actionneur électromagnétique à solénoïde, et/ou un mécanisme
à ressort, et/ou une pompe hydraulique, et/ou du gaz comprimé (CG), et/ou un volant
moteur, et/ou une machine à vapeur, et/ou une machine de Carnot et/ou un cycle de
Stirling.
3. Nébuliseur selon la revendication 2, dans lequel ladite source d'énergie (ES) (11)
comprend la source de gaz liquéfié (LG), le système comprenant en outre une sortie
de gaz liquéfié (LG) et un volume contenant du gaz liquéfié (LG) (13a) raccordé fluidiquement
à la source de gaz liquéfié (LG) et étant conçu pour contenir du gaz liquéfié (LG).
4. Nébuliseur selon l'une quelconque des revendications précédentes, dans lequel ledit
moyen formant au moins deux soupapes présente au moins une des configurations suivantes
: (a) il comprend au moins une soupape de régulation (12d) ayant un état de veille
et un état automatique et au moins deux soupapes de direction (12a, 12b) conçues pour
identifier et réguler le mouvement, la position et la direction dudit actionneur pneumatique,
et (b) il comprend une soupape de source d'énergie (ES) (12c) en raccord fluidique
avec ladite source d'énergie (ES) conçue pour réguler le mouvement dudit actionneur
pneumatique.
5. Nébuliseur selon la revendication 4, dans lequel ledit moyen formant soupapes (12)
est conçu pour libérer ladite brume de médicament sous forme de succession rapide
à un taux périodique d'environ 2,5 ml de gouttelettes dudit médicament par 2 minutes.
6. Nébuliseur selon l'une quelconque des revendications précédentes, dans lequel ledit
actionneur pneumatique (17) présente au moins une des configurations suivantes :
(a) ledit actionneur pneumatique est partiellement composé de matériau ferromagnétique
; et
(b) ledit actionneur pneumatique comprend au moins : une pompe à piston, et/ou une
turbine, et/ou un rotor et/ou un ressort à membrane gonflable.
7. Nébuliseur selon l'une quelconque des revendications 3 à 6, dans lequel ladite source
d'énergie (ES) (11) comprend la source de gaz liquéfié (LG) et dans lequel ledit actionneur
pneumatique (17) sépare ledit volume contenant du gaz liquéfié (LG) (13a) dudit volume
contenant de l'air (13b) ; ledit actionneur pneumatique facilite ledit écoulement
d'air de la dose en permettant la dilatation dudit gaz liquéfié (LG) dans ledit au
moins un volume contenant du gaz liquéfié (LG) de sa phase liquide condensée à sa
phase gazeuse dilatée.
8. Nébuliseur selon l'une quelconque des revendications précédentes, dans lequel ledit
système de buses (16) comprend au moins l'un des types de buses suivants :
une buse Venturi, une buse Laskin, des buses à écoulement annulaire à grande vitesse
et à énergie additive, et une buse à tourbillon.
9. Nébuliseur selon l'une quelconque des revendications précédentes, dans lequel ledit
angle prédéterminé est : a) inférieur à 90 °, ou b) égal à 180 °.
10. Nébuliseur selon l'une quelconque des revendications précédentes, conçu pour pulvériser
le médicament comprenant : des matériaux gazeux, et/ou des matériaux liquides, et/ou
des particules fines, et/ou des matériaux en poudre.
11. Nébuliseur selon l'une quelconque des revendications précédentes, conçu pour être
activé manuellement, semi-manuellement ou électriquement.
12. Nébuliseur selon l'une quelconque des revendications précédentes, comprenant en outre
: (a) un mécanisme de dosage de médicament comprenant une chambre à médicament (15)
et/ou une soupape de dosage (12e) ; ladite soupape de dosage étant raccordée fluidiquement
à ladite chambre à médicament, (b) une source d'alimentation comprenant : une batterie,
et/ou une source électrique, et/ou une batterie rechargeable, et/ou un moteur électrique,
(c) et/ou un moyen d'actionnement de la respiration qui répond à l'inhalation par
un sujet lorsqu'il détecte la respiration du sujet ; (d) un moyen d'actionnement de
la respiration configuré pour détecter la pression négative de l'inhalation du patient
et l'utilisation de cette détection afin de déclencher ou d'amener un écoulement de
gaz à haute pression, ledit moyen d'actionnement de la respiration comprenant au moins
un capteur de pression et un capteur de température de l'air entrant (IAT), et (e)
un moyen formant ressort en communication avec ledit actionneur pneumatique, ledit
moyen formant ressort comprenant un ressort mécanique, et/ou un ressort à gaz et/ou
une pression de gaz.
13. Nébuliseur selon la revendication 12, dans lequel ladite source d'énergie (ES) (11)
est une source de gaz liquéfié (LG) comprenant du gaz de pétrole liquéfié (GPL), ledit
moyen formant ressort étant en communication avec ledit actionneur pneumatique de
telle sorte que (i) lorsque le réservoir de gaz liquéfié (LG) est rempli dudit gaz de pétrole liquéfié
(GPL), ledit ressort est chargé ; et, (ii) l'administration dudit médicament est assurée par l'application d'une force sur ledit
actionneur, au moyen dudit ressort avec ledit gaz de pétrole liquéfié (GPL).
14. Nébuliseur selon l'une quelconque des revendications précédentes, dans lequel ledit
médicament est un liquide et lesdites première et seconde buses (220, 230 ; 310, 320)
et entrée de médicament (240 ; 330) ont des dimensions fournissant la brume de médicament
administrée en gouttelettes de médicament d'une taille comprise entre 1 µm et 7 µm.